Research Project
10198968
Hypoxic-ischemic encephalopathy (HIE) is one of the most significant causes of neurodevelopmental problems in American children, with high rates of death and major disability. The understanding of the impacts of glucose in these newborns has been limited to date by intermittent testing. The NOGIN study (Neurological Outcome of Glycemia in Neonatal Encephalopathy), using continuous glucose monitoring, has demonstrated that hyperglycemia occurs in more than 50% of HIE. While hypoglycemia was expected to be associated with brain injury, the surprising discovery has been that hyperglycemia, and not hypoglycemia, is associated with worse immediate brain function, brain injury on MRI, and motor and cognitive function at 18-month follow-up, despite adjusting for HIE severity. Standardized questionnaires also suggest increased risk for behavioural diagnoses. With the high incidence of hyperglycemia in neonatal encephalopathy and the strong evidence suggesting major additive impacts on long- term outcomes, it is now critical to clarify (1) how the findings of posterior- predominant brain injury translate to difficulties in cortical visual processing and (2) how the early findings of cognitive and behavioural concerns translate to later diagnoses by early school age. The overall objective for this study is to determine how hyperglycemia, in the context of neonatal encephalopathy, independently predicts outcomes by early school age. The specific aims include: 1. Assess how hypo- and hyperglycemia in neonatal encephalopathy impact cortical visual processing by early school age. 2. Assess how hypo- and hyperglycemia in neonatal encephalopathy impact cognitive, language, social, and behavioral function by early school age. The NOGIN study, a prospective cohort study originally aiming to determine what degree of low glucose results in hypoglycemic brain injury, with enrolment to complete in the next few months. The first subject turns 5 years old in September 2019. To achieve the current research objectives, children will be asked to return at 5 years of age for neuropsychological assessment (including WPPSI-IV, NEPSY-II, MCHAT, CBCL) and magnetoencephalography (vision tasks, resting brain network circuitry) to understand how specific levels of hyperglycemia translate to ongoing long-term deficits. By correlating specific levels of hyperglycemia in HIE in neonates with the degree of neurodevelopmental impairment, this study will help to target the management and control of hyperglycemia to decrease brain injury and improve outcomes for these newborns. The data generated will also help with early identification of newborns at greatest risk for adverse outcomes, enabling more targeted early adjunctive therapies to improve outcomes after HIE.
